The Significance of Elevated CSF Lactate S L Chow, Z J Rooney, M a Cleary, P T Clayton, J V Leonard

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1188 Arch Dis Child: first published as 10.1136/adc.2005.075317 on 21 October 2005. Downloaded from SHORT REPORT The significance of elevated CSF lactate S L Chow, Z J Rooney, M A Cleary, P T Clayton, J V Leonard ......

Arch Dis Child 2005;90:1188–1189. doi: 10.1136/adc.2005.075317

The final diagnosis of 158 patients who had a cerebrospinal 22 fluid (CSF) lactate concentration greater than 2 mmol/l was 20 ascertained. The conditions included seizures, inflammatory 18 changes, and proven metabolic disorders. For the diagnosis 16 of congenital lactic acidoses, CSF lactate should ideally be 14 measured in a seizure free patient after any acute illness. 12 10 8 s blood lactate concentrations are influenced by several 6 factors, cerebrospinal fluid (CSF) lactate concentra- 4

tions are widely used in the diagnosis of congenital CSF lactate concentration (mmol/l) 2 A 12 lactic acidoses. However, CSF lactate may also be raised in 01 32 456 78 109 association with many other illnesses including seizures,3 Diagnostic group meningitis,4 encephalitis, and cerebral ischaemia. In order to determine the value of measuring CSF lactate, we have Figure 1 CSF lactate concentrations in different diagnostic groups. reviewed the records of 158 children who attended a tertiary Open symbols: sample in acute illness. Closed symbols: sample in referral hospital with concentrations greater than or equal to chronic illness. 1: Respiratory chain disorders; 2: pyruvate 2 mmol/l. dehydrogenase deficiency; 3: other metabolic disorders (see text); 4: infection/inflammation; 5: ischaemia; 6: malignancy; 7: seizures; 8: multiple aetiology; 9: unknown. METHODS In this study, CSF lactate measurements were reviewed for the 10 year period of 1992–2002. The medical records of those Malignancy patients with values equal to or greater than 2 mmol/l were Six (4%) of the patients had malignancy. In five patients the retrieved. For patients in whom more than one CSF lactate malignancy was cerebral or meningeal in origin. The other measurement was taken, the highest value was used. patient had an adrenal neuroblastoma with cerebral metas-

Additional details were also recorded, including the patient’s tases. http://adc.bmj.com/ condition at the time of the lumbar puncture, the presence of seizures, haemodynamic status, other metabolic investiga- Other causes tions, and the final diagnosis. The project was registered with Several patients had more than one cause for raised CSF the Research and Development office and the patient details lactate concentrations. Of the 36 patients with high CSF anonymised. lactate values within 3 days of active seizures, 12 patients had other diagnoses which are likely to have contributed to the result as follows: three had a respiratory chain defect, six

RESULTS on September 30, 2021 by guest. Protected copyright. During the study period, CSF lactate was measured on 2268 an inflammatory process (two meningitis, two encephalitis, occasions. Of these measurements, 414 (18%) values from one SLE, and one post-streptococcal acute disseminated 267 patients were greater than or equal to 2 mmol/l. We were encephalomyelitis), one cerebral ischaemia, and two other able to review the records of 158 (59%) patients. CSF lactate metabolic disorders (one Gaucher’s disease and one Menke’s concentrations for patients grouped according to diagnosis syndrome). One patient with a posterior fossa medulloblas- are shown in fig 1. toma developed postoperative meningitis and another with tuberculous meningitis developed a middle cerebral artery infarct with both of these factors contributing to the raised Metabolic disorders CSF lactate values of 5.6 and 6.4 mmol/l, respectively. Forty five patients (28%) had a metabolic disorder (37 In the remaining 45 (28%) patients, no obvious cause was respiratory chain disorder, five pyruvate dehydrogenase found for the increased CSF lactate measurement. One deficiency, two Krabbe’s leukodystrophy, and one biotinidase 19 day old patient was acutely unwell with multi-organ deficiency). failure; an infection screen, urine organic acids, plasma amino acids, muscle histology, and respiratory chain enzymes Seizures failed to identify the cause of a raised CSF lactate value of In 24 patients (15%) the raised CSF lactate value was 21.9 mmol/l. Twenty nine of the 45 patients had normal attributed solely to seizure activity occurring within 3 days of metabolic investigations including muscle histology and the lumbar puncture. respiratory chain enzyme assay. Eight of these had an illness consistent with congenital lactic acidosis and, although the Intra-cranial inflammation investigations failed to confirm this, a metabolic disorder was Twenty nine patients (18%) had encephalitis, meningitis, or cerebral inflammation. Nine (6%) had cerebral ischaemia. Abbreviation: CSF, cerebrospinal fluid

www.archdischild.com ThesignificanceofelevatedCSFlactate 1189 Arch Dis Child: first published as 10.1136/adc.2005.075317 on 21 October 2005. Downloaded from still likely. Sixteen patients had metabolic investigations that level may be increased when the plasma or blood lactate did not include a muscle biopsy. In three of these patients, concentration is normal in children with electron transport definitive diagnoses were made of illnesses not known to chain defects.12If CSF lactate measurements are to be used cause raised CSF lactate values (vanishing white matter to identify patients requiring further investigation for disease, juvenile idiopathic arthritis with papillitis, and congenital lactic acidoses, the test should ideally be hereditary sensory motor neuropathy type VI). However, performed in a seizure free patient during the chronic phase the values in these patients were only marginally raised (2– of the illness, but even so it should be remembered that it 2.07). may be normal in those with a proven mitochondrial disorder.5 DISCUSSION Great Ormond Street Hospital is a tertiary referral children’s ...... hospital and the specialist nature of the hospital will have Authors’ affiliations influenced the diagnoses and frequency of raised CSF lactate S L Chow, Z J Rooney, M A Cleary, P T Clayton, J V Leonard, Metabolic values. Furthermore, only 60% of the notes were reviewed. Unit, Great Ormond Street Hospital for Children, London, UK P T Clayton, J V Leonard, Biochemistry, Endocrinology and Metabolism Nevertheless, the results show that in the patients investi- Unit, Institute of Child Health, University College London, London, UK gated a CSF lactate value greater than 2 mmol/l is not uncommon as 18% of all values were above this concentra- Competing interests: none declared tion. Correspondence to: Professor James Leonard, 40A Bagley Wood Road, Our study confirms that CSF lactate concentrations can be Kennington, Oxford, OX1 5LY, UK; [email protected] raised in association with seizures, meningitis or encephalitis, cerebral ischaemia, malignancy, and other metabolic dis- Accepted 21 July 2005 orders and is not specific for congenital lactic acidoses. Of patients who were acutely unwell at the time of the REFERENCES lumbar puncture, only 9% were found to have congenital 1 Hutchesson A, Preece MA, Gray G, et al. Measurement of lactate in lactic acidosis, compared to 34% of patients who were in the cerebrospinal fluid in investigation of metabolic disease. Clin Chem chronic phase of their illness. CSF lactate concentration is 1997;43(1):158–61. less specific for congenital lactic acidoses in patients who are 2 Stacpoole PW, Bunch ST, Neiberger RE, et al. The importance of acutely unwell. cerebrospinal fluid lactate in the evaluation of congenital lactic acidosis. J Pediatr 1999;134(1):99–102. Measurement of blood lactate is often used as a first 3 Calabrese VP, Gruemer HD, James K, et al. Cerebrospinal fluid lactate levels line assessment of those with presumed congenital lactic and prognosis in status epilepticus. Epilepsia 1991;32(6):816–21. acidosis. However, it is recognised that blood lactate levels 4 Eross J, Silink M, Dorman D. Cerebrospinal fluid lactic acidosis in bacterial meningitis. Arch Dis Child 1981;56(9):692–8. are notoriously variable, being affected by many factors 5 Smeitink JAM. Mitichondrial disorders: clinical presentation and diagnostic including muscle movement. Furthermore, the CSF lactate dilemmas. J Inherit Metab Dis 2003;26:199–207.

IMAGES IN PAEDIATRICS...... http://adc.bmj.com/ doi: 10.1136/adc.2005.083261 Muscle fibre type grouping in high resolution ultrasound 5 year old boy with motor retardation presented with prox- Aimal weakness maximal in the lower limbs and generalised muscular on September 30, 2021 by guest. Protected copyright. atrophy. The deep tendon reflexes were absent. Tremor or fasciculations were not seen. The muscles of the boy were examined by a high resolution ultrasound system and real time compound imaging. The deep muscles consisted of atrophic fibres (bright areas in fig 1) with groups of hypertrophic fibres (black areas in fig 2). The analysis of the survival motor neurone (SMN) 1 gene resulted in a homozygous deletion Figure 2 Schematic drawing of fig 1 with of exon 7 and 8 confirming the diag- Figure 1 Cross ultrasound section of m. vastus intermedius showing the groups of hypertrophic black areas showing the groups of hypertrophic nosis of spinal muscular atrophy. among the atrophic muscle fibres. muscle fibres. Muscle fibres of the denervated motor unit atrophy. Reinnervation by collateral sprouting results in grouping of hyper- findings can be compared to histological Correspondence to: Dr A van Baalen, trophic fibres with the same histo- findings. Department of Neuropediatrics, chemical type, commonly called ‘‘type Universita¨tsklinikum Schleswig-Holstein, Schwanenweg 20, Kiel 24105, Germany; grouping’’. A van Baalen, U Stephani Using this new ultrasound tech- Universita¨tsklinikum Schleswig-Holstein, Kiel, [email protected] nique, ultrasound morphological Germany Competing interests: none declared